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GeneBe

3-27284960-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_001394966.1(NEK10):c.1791T>C(p.Asn597=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,586,054 control chromosomes in the GnomAD database, including 54,845 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.24 ( 4675 hom., cov: 32)
Exomes 𝑓: 0.26 ( 50170 hom. )

Consequence

NEK10
NM_001394966.1 splice_region, synonymous

Scores

2
Splicing: ADA: 0.4034
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.20
Variant links:
Genes affected
NEK10 (HGNC:18592): (NIMA related kinase 10) Enables protein kinase activity. Involved in several processes, including mucociliary clearance; positive regulation of protein phosphorylation; and regulation of ERK1 and ERK2 cascade. Part of protein kinase complex. Implicated in primary ciliary dyskinesia 44. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-27284960-A-G is Benign according to our data. Variant chr3-27284960-A-G is described in ClinVar as [Benign]. Clinvar id is 1325895.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=3.2 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NEK10NM_001394966.1 linkuse as main transcriptc.1791T>C p.Asn597= splice_region_variant, synonymous_variant 21/36 ENST00000691995.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NEK10ENST00000691995.1 linkuse as main transcriptc.1791T>C p.Asn597= splice_region_variant, synonymous_variant 21/36 NM_001394966.1 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.238
AC:
36165
AN:
152040
Hom.:
4675
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.140
Gnomad AMI
AF:
0.347
Gnomad AMR
AF:
0.342
Gnomad ASJ
AF:
0.337
Gnomad EAS
AF:
0.0951
Gnomad SAS
AF:
0.295
Gnomad FIN
AF:
0.282
Gnomad MID
AF:
0.380
Gnomad NFE
AF:
0.266
Gnomad OTH
AF:
0.270
GnomAD3 exomes
AF:
0.276
AC:
63652
AN:
230822
Hom.:
9364
AF XY:
0.280
AC XY:
35078
AN XY:
125424
show subpopulations
Gnomad AFR exome
AF:
0.136
Gnomad AMR exome
AF:
0.388
Gnomad ASJ exome
AF:
0.346
Gnomad EAS exome
AF:
0.103
Gnomad SAS exome
AF:
0.306
Gnomad FIN exome
AF:
0.279
Gnomad NFE exome
AF:
0.278
Gnomad OTH exome
AF:
0.280
GnomAD4 exome
AF:
0.258
AC:
369673
AN:
1433896
Hom.:
50170
Cov.:
29
AF XY:
0.261
AC XY:
186173
AN XY:
713844
show subpopulations
Gnomad4 AFR exome
AF:
0.137
Gnomad4 AMR exome
AF:
0.386
Gnomad4 ASJ exome
AF:
0.338
Gnomad4 EAS exome
AF:
0.0911
Gnomad4 SAS exome
AF:
0.304
Gnomad4 FIN exome
AF:
0.278
Gnomad4 NFE exome
AF:
0.256
Gnomad4 OTH exome
AF:
0.256
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.238
AC:
36174
AN:
152158
Hom.:
4675
Cov.:
32
AF XY:
0.242
AC XY:
18024
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.140
Gnomad4 AMR
AF:
0.342
Gnomad4 ASJ
AF:
0.337
Gnomad4 EAS
AF:
0.0954
Gnomad4 SAS
AF:
0.294
Gnomad4 FIN
AF:
0.282
Gnomad4 NFE
AF:
0.266
Gnomad4 OTH
AF:
0.267
Alfa
AF:
0.271
Hom.:
12489
Bravo
AF:
0.236
Asia WGS
AF:
0.186
AC:
649
AN:
3478
EpiCase
AF:
0.292
EpiControl
AF:
0.294

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Ciliary dyskinesia, primary, 44 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 05, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
Cadd
Benign
12
Dann
Benign
0.89

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.40
dbscSNV1_RF
Benign
0.16
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10510594; hg19: chr3-27326451; COSMIC: COSV58281604; COSMIC: COSV58281604; API